Development and refinement of functional properties of adult-born olfactory bulb neurons

项目摘要 感觉系统必须是可塑性的，以便在整个生命周期中进行学习;然而，大脑区域 参与处理感觉信息的神经元在正常衰老和 并且与神经精神和神经变性疾病相一致。例如，嗅觉缺陷是 估计影响了美国一半以上的老年人口。的一个有前途的功能， 然而，嗅觉系统是其终身可塑性的广泛能力。在啮齿动物中，嗅球（OB）是 由于持续的神经发生，这是成人大脑中最具可塑性的区域。成人颗粒细胞（abGCs） 是成年人出生的神经元中数量最多的群体，在它们的成熟过程中， 与现有的细胞和集成到OB电路。然而，关于这方面的信息仍然有限。 abGC对体内刺激的反应的发展。本项目旨在利用纵向在体多光子 个体abGC的气味诱发反应的钙成像以表征（1）abGC何时首次成为 对嗅觉刺激的反应以及单个神经元的反应如何随着细胞的变化而变化， 成熟和（2）如何在嗅觉学习的背景下修改这个过程。初步数据 表明在种群水平上，abGCs在其发育早期对气味更敏感。这 支持这一假设，即abGCs最初的广泛代表性可能会得到改善，以提高其选择性 在它们成熟的时候会有特殊的气味。随着时间的推移，分析识别出的细胞的气味响应曲线将允许 研究单个细胞的气味反应强度、稳定性和气味选择性的时间过程 在单个细胞水平上。此外，在一个关键时期，在一个操作性行为任务中训练小鼠， abGC的队列将提供对气味暴露和气味奖励协会对 abGC反应的稳定性和普遍性。总之，这些实验将提供重要的见解， 成人出生的神经元整合到现有电路中的过程以及可能的机制， 这个过程可以通过学习来修改，以便增强感觉处理。

Project Summary Sensory systems must be plastic in order to allow learning throughout the lifespan; however, brain regions involved in processing sensory information undergo a significant decline in plasticity during both normal aging and in concert with neuropsychiatric and neurodegenerative diseases. For example, olfactory deficits are estimated to affect more than half of the elderly population in the United States. One promising feature of the olfactory system, however, is its extensive capability for lifelong plasticity. In rodents, the olfactory bulb (OB) is one of the most plastic areas of the adult brain due to ongoing neurogenesis. Adult-born granule cells (abGCs) are the most numerous population of adult-born neurons, and during their maturation, they develop synapses with existing cells and integrate into the OB circuit. However, there is still limited information about the development of abGCs’ responses to stimuli in vivo. This project aims to use longitudinal in vivo multiphoton calcium imaging of individual abGCs’ odor-evoked responses to characterize (1) when abGCs first become responsive to olfactory stimuli and how the responses of individual neurons change over time as the cells mature and (2) how this process may be modified in the context of olfactory learning. Preliminary data indicates that on a population level, abGCs are more responsive to odors early during their development. This supports the hypothesis that abGCs’ initially broad representations may be refined to enhance their selectivity for particular odors as they mature. Analyzing the odor response profiles of identified cells over time will allow the investigation of the timecourse of an individual cell’s odor response magnitude, stability and odor selectivity on a single cell level. In addition, training mice in an operant behavioral task during the critical period of a cohort of abGCs will provide insight into the effects of odor exposure and odor-reward associations on the stability and prevalence of abGC responses. Together, these experiments will provide important insights into the process by which adult-born neurons integrate into an existing circuit and possible mechanisms by which this process may be modified by learning in order to enhance sensory processing.